Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen

Phase 2

Terminated

• Conditions: NSCLC
• Interventions: Drug: Pimivalimab; Drug: Vopratelimab

• Registration Number: NCT04549025
• Lead Sponsor: Jounce Therapeutics, Inc.

Brief Summary

This is a Phase 2, open-label study to evaluate PD-1 inhibitor pimivalimab (JTX-4014) alone and in combination with vopratelimab (JTX-2011), an ICOS agonist, in biomarker-selected adult subjects with metastatic NSCLC who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum-based chemotherapy regimen.

Detailed Description

Pimivalimab is a fully human IgG4 monoclonal antibody designed to specifically bind to programmed cell death receptor protein-1 (PD-1) and block its interaction with its ligands, programmed cell death receptor protein-1 ligand 1 (PD-L1) and programmed cell death receptor protein-1 ligand 2 (PD-L2), to augment anti-tumor T cell activity. Vopratelimab is an agonist monoclonal antibody that specifically binds to the Inducible CO-Stimulator of T cells (ICOS) to generate an anti-tumor immune response. This is a Phase 2, open label study to evaluate the efficacy, safety, tolerability of pimivalimab alone and in combination with vopratelimab in biomarker-selected adult subjects with metastatic non-small cell lung cancer (NSCLC) who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum-based chemotherapy regimen.

Study Timeline

• Study First Submitted: 2020-09-01
• Study First Submitted QC: 2020-09-08
• Study First Posted: 2020-09-16
• Study Start: 2020-10-19
• Primary Completion: 2024-04-25
• Study Completion: 2024-04-25
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-21
• Last Update Posted: 2024-05-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures;

2. Histologically or cytologically confirmed diagnosis of NSCLC with evaluable or measurable disease according to RECIST v1.1 with at least 1 measurable lesion;

3. Confirmed tumor RNA signature score in accordance with the study protocol;

4. Previously treated for locally advanced or metastatic NSCLC with 1 prior systemic antineoplastic platinum-containing regimen. Regimen should consist of chemotherapy or with bevacizumab;

5. Age of ≥18 years;

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

7. Predicted life expectancy of ≥ 3months;

8. Specified laboratory values in accordance with the study protocol;

9. If with medical history of the following, eligibility should be discussed with the Medical Monitor:

   1. Prior biliary tract disorders (based on Medical Dictionary for Regulatory Activities [MedDRA] system organ class of Hepatobiliary disorders and MedDRA high-level terms of Obstructive bile duct disorders, Hepatic vascular disorders, and Structural and other bile duct disorders);
   2. Portal hypertension and/or hepatic vascular disorders;

10. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned Cycle 1, Day 1 (C1D1) and a negative urine or serum pregnancy test on C1D1. In addition, the WOCBP must be willing to complete a urine or serum pregnancy test prior to each dose of either study drug;

11. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration. Highly effective methods of birth control are defined as those that, alone or in combination, result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.

Exclusion Criteria

1. Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational;

2. Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting;

3. Chemotherapy <28 days prior to planned C1D1

4. Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor monoclonal antibody (mAb) at any time, including pimivalimab; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy;

5. Organ transplantation, including allogenic or autologous stem cell transplantation;

6. Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease):

   1. Biologic therapy
   2. Targeted therapy, with the exception of bevacizumab if administered in combination with a platinum-based chemotherapy regimen as first line treatment

7. Positive test for any of the following epidermal growth factor receptor gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q;

8. The following toxicity history:

   1. Ongoing toxicity attributed to prior therapy that was Grade >1 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE); Exceptions: Grade >1 toxicities that, in the opinion of the Investigator, should not exclude the subject (e.g., alopecia, Grade 2 neuropathy, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement therapy) and are approved by the Medical Monitor;
   2. History of pneumonitis or interstitial lung disease;
   3. Symptomatic ascites or pleural effusion (subjects who are clinically stable for >3 months following treatment for these conditions [including therapeutic thoraco- or paracentesis] are eligible);
   4. If with medical history of the following, eligibility should be discussed with the Medical Monitor: colitis, hepatitis, nephritis, skin reactions, or encephalitis;

9. Known severe intolerance or life-threatening hypersensitivity reactions to humanized mAbs or IV Ig preparations; any history of anaphylaxis; prior history of human anti-human antibody response; or known allergy to any of the study drugs (including their analogues or excipients [L-Histidine, mannitol, sodium chloride, or polysorbate 80]);

10. Major surgery (excluding minor procedures, e.g., placement of vascular access, gastrointestinal/biliary stent, and biopsy) < 4 weeks prior to planned C1D1;

11. Prior whole brain radiation;

12. Subjects with the following should be reviewed with the Medical Monitor prior to enrollment:

    1. Brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation;
    2. Radiation (other than whole brain radiation) has been or will be administered <21 days prior to planned C1D1;

13. Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis B, C, or human immunodeficiency virus (testing not required);

14. Women who are pregnant, breastfeeding, or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study;

15. Concurrent second malignancy;

16. An active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents at a dose of ≥10 mg/day of prednisone equivalent. Subjects who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism who are stable on hormone replacement therapy will not be excluded from the study;

17. Medical or social condition that, in the opinion of the Investigator, might place the subject at an increased risk, adversely affect compliance, or confound safety or other clinical study data interpretation;

18. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Monotherapy Cohort 1 (MC1)	Pimivalimab	Enrolled patients will receive 1000 mg pimivalimab (JTX-4014) administered alone every 6 weeks (q6w).
Combination Therapy Cohort 1 (CC1)	Pimivalimab	For Cycle 1, enrolled patients will receive 0.1 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.
Combination Therapy Cohort 1 (CC1)	Vopratelimab	For Cycle 1, enrolled patients will receive 0.1 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.
Combination Therapy Cohort 2 (CC2)	Pimivalimab	For Cycle 1, enrolled patients will receive 0.03 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.
Combination Therapy Cohort 2 (CC2)	Vopratelimab	For Cycle 1, enrolled patients will receive 0.03 mg/kg vopratelimab (JTX-2011) on Day 1, followed by 1000 mg pimivalimab (JTX-4014) on Day 8. For Cycle 2 and beyond, vopratelimab and pimivalimab will be administered in combination (on Day 1) q6w.

Primary Outcome Measures

Name	Time	Method
Change in measurable lesion size	over 9 and 18 weeks (average)	Mean percent change from baseline tumor size of all measurable existing and new lesions

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic properties of pimivalimab and vopratelimab - volume of distribution (amount of drug in the body divided by the plasma drug concentration)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Overall response rate (ORR)	up to 24 months	ORR (percentage of subjects with complete response \[CR\] + partial response \[PR\]) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Progression-free survival (PFS)	up to 24 months	PFS according to RECIST v1.1
Landmark PFS rate	9 months	Landmark PFS rate at 9 months according to RECIST v1.1
Disease control rate (DCR)	up to 24 months	DCR (confirmed CR + confirmed PR + unconfirmed stable disease \[SD\]) according to RECIST v1.1
Duration of response (DOR)	up to 24 months	DOR in months according to RECIST v1.1
Overall survival (OS)	up to 24 months
Treatment-emergent adverse events (TEAEs)	up to 24 months	Incidence and grade of TEAEs
Pharmacokinetic properties of pimivalimab and vopratelimab - Cmax (maximum observed concentration)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Pharmacokinetic properties of pimivalimab and vopratelimab - Tmax (time of first occurrence of Cmax)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Pharmacokinetic properties of pimivalimab and vopratelimab - AUClast (area under the concentration-time curve from time zero to the last measurable concentration)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Pharmacokinetic properties of pimivalimab and vopratelimab - half-life (time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Pharmacokinetic properties of pimivalimab and vopratelimab - clearance (efficiency of drug elimination)	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Incidence of neutralizing antibodies (NAbs) to either pimivalimab or vopratelimab	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Incidence of anti-drug antibodies (ADAs) to either pimivalimab or vopratelimab	Cycle 1 through Cycle 6 (each cycle is 6 weeks)
Association of baseline tumor RNA signature score with clinical outcomes	up to 24 months	Change in measurable lesion size for patients with elevated tumor RNA signature score (i.e., tumor inflammation signature (TIS) vopra score ≥ 7.9)

Trial Locations

Locations (72)

Kyiv Railway Clinical Hospital #3 of Branch Health Center of the PJSC Ukrainian Railway; 🇺🇦 Kyiv, Ukraine

Arensia Tbilisi - PPDS; 🇬🇪 Tbilisi, Georgia

Veszprem Megyei Tudogyogyintezet; 🇭🇺 Farkasgyepű, Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz; 🇭🇺 Székesfehérvár, Hungary

Riga East Clinical University Hospital, Latvian Oncology Center; 🇱🇻 Riga, Latvia

Chelyabinsk Regional Clinical Oncology Dispensary; 🇷🇺 Chelyabinsk, Russian Federation

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic; 🇷🇺 Kazan, Russian Federation

Oncology Center Sfantul Nectarie; 🇷🇴 Craiova, Romania

Clinical Center University of Sarajevo; 🇧🇦 Sarajevo, Bosnia and Herzegovina

Ryazan State Medical University n.a. I.P. Pavlov; 🇷🇺 Ryazan', Russian Federation

Volgograd Regional Clinical Oncology Dispensary; 🇷🇺 Volgograd, Russian Federation

Vychodoslovensky onkologicky ustav, a.s.; 🇸🇰 Košice, Slovakia

University Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Institute of Lung Diseases Vojvodina; 🇷🇸 Sremska Kamenica, Serbia

Adana Sehir Egitim ve Arastirma Hastanesi; 🇹🇷 Adana, Turkey

Inonu University Faculty of Medicine Turgut Ozal Medical Center; 🇹🇷 Malatya, Turkey

Communal Nonprofit Enterprise Regional Center of Oncology; 🇺🇦 Kharkiv, Ukraine

Communal Nonprofit Enterprise Khmelnytskyi Regional Antitumor Center of Khmelnytskyi Regional Council; 🇺🇦 Khmelnytskyi, Ukraine

Clinic of National Institute of Cancer; 🇺🇦 Kyiv, Ukraine

Akdeniz University Medical Faculty Hospital; 🇹🇷 Antalya, Turkey

Municipal Nonprofit Enterprise SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC; 🇺🇦 Ivano-Frankivs'k, Ukraine

Arensia Kapitanivka - PPDS; 🇺🇦 Kapitanivka, Ukraine

Ege Universitesi Tip Fakultesi Hastanesi; 🇹🇷 İzmir, Turkey

Communal Nonprofit Enterprise Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of ChOC; 🇺🇦 Cherkasy, Ukraine

Medical Center of LLC ARENSIA Exploratory Medicine; 🇺🇦 Kyiv, Ukraine

Medical and diagnostic center of MediX-Ray International Group LLC Israeli Oncology Hospital LISOD; 🇺🇦 Obukhiv, Ukraine

Mordovia State University; 🇷🇺 Saransk, Russian Federation

JSC "Current medical technologies"; 🇷🇺 Saint Petersburg, Russian Federation

Research Oncology Institute of Tomsk Scientific Center; 🇷🇺 Tomsk, Russian Federation

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda; 🇧🇬 Sofia, Bulgaria

Minsk City Clinical Oncology Dispensary; 🇧🇾 Minsk, Belarus

N. N. Alexandrov National Cancer Centre; 🇧🇾 Minsk, Belarus

University Clinical Center of the Republic of Srpska; 🇧🇦 Banja Luka, Bosnia and Herzegovina

Multiprofile Hospital for Active Treatment - Dobrich AD; 🇧🇬 Dobrich, Bulgaria

Multiprofile Hospital for Active Treatment Serdika EOOD; 🇧🇬 Sofia, Bulgaria

Clinical Hospital Centre Osijek; 🇭🇷 Osijek, Croatia

Pauls Stradins Clinical University Hospital; 🇱🇻 Riga, Latvia

General Hospital Pula; 🇭🇷 Pula, Croatia

Bács-Kiskun Varmegyei Oktatokorhaz; 🇭🇺 Kecskemét, Hungary

Arensia Chisinau - PPDS; 🇲🇩 Chisinau, Moldova, Republic of

Affidea Romania SRL; 🇷🇴 Bucharest, Romania

Vitamed Multidisciplinary Medical Center; 🇷🇺 Moscow, Russian Federation

Hacettepe University Medical Faculty Hospital; 🇹🇷 Ankara, Turkey

Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi Hastane - Hematoloji Bilim Dali; 🇹🇷 Edirne, Turkey

Istanbul University Cerrahpasa Medical Faculty Hospital; 🇹🇷 Istanbul, Turkey

Izmir Ekonomi University Medical Point Hospital; 🇹🇷 İzmir, Turkey

T.C. Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin City Hospital; 🇹🇷 Istanbul, Turkey

ME Volyn Regional Clinical Hospital of the Volyn Regional Council Regional Medical Oncology Centre; 🇺🇦 Luts'k, Ukraine

Clinical Oncology Dispensary; 🇷🇺 Omsk, Russian Federation

Arkhangelsk Regional Clinical Oncology Dispensary; 🇷🇺 Arkhangel'sk, Russian Federation

Narodny onkologicky - PPDS; 🇸🇰 Bratislava, Slovakia

PMI Euromedservice; 🇷🇺 Pushkin, Russian Federation

Regional Clinical Oncology Hospital; 🇷🇺 Yaroslavl, Russian Federation

Institute for Oncology and Radiology of Serbia - PPDS; 🇷🇸 Belgrade, Serbia

University Clinical Center of Serbia - PPDS; 🇷🇸 Belgrade, Serbia

Clinical Hospital Center Bezanijska Kosa; 🇷🇸 Belgrade, Serbia

SI Institute of Medical Radiology and Oncology n.a. S.P. Hryhoriev of NAMS of Ukraine; 🇺🇦 Kharkiv, Ukraine

MNPE Central City Clinical Hospital of Uzhhorod City Council; 🇺🇦 Uzhhorod, Ukraine

University Hospital of Split; 🇭🇷 Split, Croatia

Multiprofile Hospital for Active Treatment - Uni Hospital OOD; 🇧🇬 Panagyurishte, Bulgaria

Complex Oncology Center Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Klinicki bolnicki centar Zagreb; 🇭🇷 Zagreb, Croatia

Prof Dr I Chiricuta Institute of Oncology; 🇷🇴 Cluj-Napoca, Romania

Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta; 🇷🇴 Constanţa, Romania

Krasnoyarsk Regional Oncology Center n.a. A.I. Kryzhanovskiy; 🇷🇺 Krasnoyarsk, Russian Federation

Kursk Regional Oncology Centre; 🇷🇺 Kursk, Russian Federation

Nizhniy Novgorod City Oncology Center; 🇷🇺 Nizhny Novgorod, Russian Federation

First St. Petersburg State Medical University n.a. I.P Pavlov; 🇷🇺 Saint Petersburg, Russian Federation

GBUZ St. Petersburg Clinical Research Center of Specialized Types of Care Oncology n.a. Napalkova; 🇷🇺 Saint Petersburg, Russian Federation

Communal Nonprofit Enterprise City Clinical Hospital #4 of Dnipro City Council; 🇺🇦 Dnipro, Ukraine

Private Enterprise Private Manufacturing Company Acinus; 🇺🇦 Kropyvnytskyi, Ukraine

Communal Nonprofit Enterprise Kyiv City Clinical Oncological Center; 🇺🇦 Kyiv, Ukraine